Mast cell FcεRI-induced early growth response 2 regulates CC chemokine ligand 1-dependent CD4⁺ T cell migration

Mast cells are well positioned in host tissue for detecting environmental signals, including allergens, leading to activation of the high-affinity IgE receptor FcεRI, and initiating a signaling cascade that perpetuates the production of biologically potent mediators, including chemokines. We have identified a novel target of mast cell FcεRI activity in the transcription factor early growth response 2 (Egr2) and sought to characterize its function therein. Egr2 was transiently activated following FcεRI-mediated signaling, targeted the promoter of the chemokine CCL1, and was critical for allergen-induced mast cell CCL1 production. Egr2-deficient mast cells were incapable of directing CD4⁺ T cell migration via the CCL1-CCR8 axis. In a model of allergic asthma, reconstitution of mast cell-deficient mice with Egr2-deficient mast cells demonstrated that mast cell Egr2 was essential for migration of CD4⁺ T cells to the inflamed lung. These findings position Egr2 as a critical regulator of mast cell-directed CD4+ T cell migration.